Multicomponent Reaction to Construct Spirocyclic Oxindoles with a Michael (Triple Michael)/Cyclization Cascade Sequence as the Key Step

Authors

  • Dr. Jian Li,

    Corresponding author
    1. Department of Chemistry, Shanghai University, 99 Shangda Road, Shanghai, 200444 (P.R. China), Fax: (+86) 21-66132408
    • Department of Chemistry, Shanghai University, 99 Shangda Road, Shanghai, 200444 (P.R. China), Fax: (+86) 21-66132408
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  • Ning Wang,

    1. Department of Chemistry, Shanghai University, 99 Shangda Road, Shanghai, 200444 (P.R. China), Fax: (+86) 21-66132408
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  • Dr. Chunju Li,

    1. Department of Chemistry, Shanghai University, 99 Shangda Road, Shanghai, 200444 (P.R. China), Fax: (+86) 21-66132408
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  • Prof. Dr. Xueshun Jia

    Corresponding author
    1. Department of Chemistry, Shanghai University, 99 Shangda Road, Shanghai, 200444 (P.R. China), Fax: (+86) 21-66132408
    2. State Key Laboratory of Applied Organic Chemistry, Lanzhou University, Lanzhou, 730000 (P.R. China)
    • Department of Chemistry, Shanghai University, 99 Shangda Road, Shanghai, 200444 (P.R. China), Fax: (+86) 21-66132408
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Abstract

Multicomponent cycloadditions with readily available isocyanides, allenoates, and isatylidene malononitriles are disclosed. This reaction, which does not require the aid of any catalyst, allows the efficient syntheses of spirocyclic oxindoles with excellent regioselectivity. Reactions with ethyl 2,3-butadienoate and various structurally diverse α- and γ-substituted allenoates are also fully explored. Remarkably, we have shown that the usual three-component process can be further developed into an unprecedented four-component cycloaddition in the presence of water, which provides a new strategy to access highly unusual tricyclic oxindoles. From a synthetic point of view, this protocol is very interesting considering the high level of complexity reached in one step. The mechanism is thought to proceed by a triple Michael/cyclization process by using allenoate as a three carbon atom component (3 C). Furthermore, multicomponent reaction with γ-substituted allenoate also results in a very interesting conversion. In such cases, the unusual cleavage of the “C[DOUBLE BOND]C” double bond of isatylidene malononitrile and one of the “C[DOUBLE BOND]C” double bonds of allenoate is always observed.

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